Oncotarget

Research Papers:

Identification of a novel HIV-1-neutralizing antibody from a CRF07_BC-infected Chinese donor

Youxiang Sun, Yuanyuan Qiao, Yuanmei Zhu, Huihui Chong and Yuxian He _

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Oncotarget. 2017; 8:63047-63063. https://doi.org/10.18632/oncotarget.18594

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Abstract

Youxiang Sun1,2,*, Yuanyuan Qiao1,2,*, Yuanmei Zhu1,2, Huihui Chong1,2 and Yuxian He1,2

1MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China

2Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China

*These authors have equally contributed to this work

Correspondence to

Yuxian He, email: [email protected]

Keywords: HIV-1, neutralizing antibody, epitope, vaccine

Received: May 07, 2017    Accepted: May 29, 2017    Published: June 21, 2017

ABSTRACT

The identification of human monoclonal antibodies (mAbs) able to neutralize a broad spectrum of primary HIV-1 isolates is highly important for understanding the immune response of HIV-1 infection and developing vaccines and therapeutics. In this study, we isolated a novel human mAb termed Y498 from a phage display antibody library constructed with the PBMC samples of a CRF07_BC-infected Chinese donor whose sera exhibited broadly neutralizing activity. Y498 cross-reacted with diverse Env antigens and neutralized 30% of 70 tested HIV-1 isolates. It efficiently blocked the binding of soluble CD4 to gp120 and competed with the CD4-binding site (CD4bs)-specific mAbs. By combining molecular docking and site-directed mutagenesis, the epitope of Y498 was characterized to contain three antigenic sites on gp120, including the CD4 binding loop in C3, the β23 in C4 and the β24-α5 in C5, which overlap the binding sites of CD4 and CD4bs-directed mAbs (b12, VRC01, A16). Therefore, Y498 is a novel neutralizing human mAb targeting a conformation-dependent CD4bs-based epitope, and its isolation and characterization could provide helpful information for elucidating human immune response to HIV-1 infection and designing effective vaccines and immunotherapeutics.


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